Glucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited regarding the associations between glucocorticoid use and breast cancer risk. We investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade. Among 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk [HR = 0.94 (0.85–1.05)]; however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer [HRinsitu = 1.34 (1.01–1.78); HRinvasive = 0.86 (0.76–0.97); Phomogeneity = 0.01]. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer [HRER+ = 0.82 (0.72–0.94); HRER− = 1.21 (0.88–1.66); Phomogeneity = 0.03]; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86); HRstage3/4 = 1.49 (1.02–2.20); Phomogeneity = 0.01]. This study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage.

中文翻译：

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在绝经后妇女的前瞻性队列中使用全身性糖皮质激素和患乳腺癌的风险

理论上，糖皮质激素可以通过抗炎作用降低乳腺癌风险，或通过免疫抑制增加风险。然而，关于糖皮质激素使用与乳腺癌风险之间关联的流行病学证据有限。我们调查了 E3N 队列中全身性糖皮质激素使用与乳腺癌发病率之间的关联，该队列包括 98,995 名女性，这些女性通过重复问卷收集的各种特征信息与 2004 年的药物报销数据相辅相成。自 2004 年 1 月 1 日以来的前 3 个月期间，被定义为暴露。我们将暴露视为一个随时间变化的参数，我们使用多变量 Cox 回归模型来估计乳腺癌的风险比 (HR)。我们使用特定原因的风险方法进行了竞争风险分析，以研究肿瘤亚型/分期/等级的异质性。在 62,512 名绝经后妇女（纳入时的中位年龄为 63 岁）中，2864 名在中位随访 9 年（2004 年至 2014 年）期间发展为乳腺癌。与非暴露相比，糖皮质激素暴露与总体乳腺癌风险无关 [HR = 0.94 (0.85–1.05)]；然而，它与较高的原位乳腺癌风险和较低的浸润性乳腺癌风险相关 [HRinsitu = 1.34 (1.01–1.78); HR侵袭 = 0.86 (0.76–0.97); 同质性 = 0.01]。关于浸润性乳腺癌的风险，糖皮质激素暴露与雌激素受体 (ER) 阳性乳腺癌呈负相关 [HRER+ = 0.82 (0.72–0.94)；HRER− = 1.21 (0.88–1.66)；同质性 = 0.03]; 它也与 1 期或 2 期肿瘤的风险呈负相关，但与 3/4 期乳腺癌的风险呈正相关 [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86)；HRstage3/4 = 1.49 (1.02–2.20)；同质性 = 0.01]。这项研究表明，全身性糖皮质激素使用与乳腺癌风险之间的关联可能因肿瘤亚型和分期而异。